Ocular infection of guinea pigs with C. psittaci GPIC causes a self-limiting conjunctivitis similar to that observed during primary ocular infections of humans infected with C. trachomatis. We have used a guinea pig model to study the immunological responses elicited by an ocular chlamydial infection. The transient protective immunity that develops after primary infection is thought to be mediated by local antibody. We have begun to analyze tears and serum for antibodies directed at particular chlamydial antigens. This may allow us to correlate antibody response to a particular antigen and protection. Preliminary data indicate that immune sera contain antibodies reactive to many chlamydial antigens, whereas antibodies found in immune tears react primarily with proteins having molecular weights of 92 kDa, 84 kDa, 57 kDa, and MOMP. IgG2 was found to be the predominant isotype of chlamydial-specific serum antibodies, whereas tears contained approximately equal titers of IgA and IgG2. An important sequelae of repeated or recurrent chlamydial infections is chronic inflammation, which leads to irreversible tissue damage. We have identified and purified a 57-kDa genus- specific chlamydial antigen that elicits an ocular delayed hypersensitive response in immune guinea pigs. Furthermore, when cells persistently infected with Chlamydia are maintained in vitro, this antigen is released into the medium. The delayed hypersensitivity response elicited by antigen purified from culture supernatants of persistently infected cells is indistinguishable from that elicited by antigen purified from chlamydial EBs. The 57-kDa chlamydial protein is a potent stimulator of ocular delayed hypersensitivity and may contribute to the chronic inflammation that is observed in human chlamydial disease.